Matches in SemOpenAlex for { <https://semopenalex.org/work/W2510223785> ?p ?o ?g. }
- W2510223785 abstract "Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation. We found that prolonged inhibition of DNA methyltransferase (DNMT) activity increased intrinsic membrane excitability of cultured cortical pyramidal neurons. Knockdown of the cytosine demethylase TET1 or inhibition of RNA polymerase blocked the increased membrane excitability caused by DNMT inhibition, suggesting that this effect was mediated by subsequent cytosine demethylation and de novo transcription. Prolonged DNMT inhibition blunted the medium component of the after-hyperpolarization potential, an effect that would increase neuronal excitability, and was associated with reduced expression of the genes encoding small-conductance Ca(2+)-activated K(+) (SK) channels. Furthermore, the specific SK channel blocker apamin increased neuronal excitability but was ineffective after DNMT inhibition. Our results suggested that DNMT inhibition enables transcriptional changes that culminate in decreased expression of SK channel-encoding genes and decreased activity of SK channels, thus providing a mechanism for the regulation of neuronal intrinsic membrane excitability by dynamic DNA cytosine methylation. This study has implications for human neurological and psychiatric diseases associated with dysregulated intrinsic excitability." @default.
- W2510223785 created "2016-09-16" @default.
- W2510223785 creator A5032220013 @default.
- W2510223785 creator A5041900573 @default.
- W2510223785 creator A5053267978 @default.
- W2510223785 creator A5060368461 @default.
- W2510223785 creator A5063005937 @default.
- W2510223785 creator A5071337074 @default.
- W2510223785 creator A5085179678 @default.
- W2510223785 date "2016-08-23" @default.
- W2510223785 modified "2023-10-14" @default.
- W2510223785 title "Dynamic DNA methylation regulates neuronal intrinsic membrane excitability" @default.
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